Infective endocarditis is the most common serious and life-threatening cardiac infection in the United States. The number of cases is expected to increase because of the increasing numbers of intravenous drug users and elderly individuals with underlying valvular degenerative changes. Both groups are at risk for the development of the disease. Over 50% of all cases of infective endocarditis are caused by oral streptococci of the mitis group and the mutans group of streptococci, where historically many members were called viridans streptococci. The generally nonnivasive Streptococcus mutans is a member of the dental caries-causing mutans group streptococci and is the most frequent species of the mutans streptococci isolated from the oral cavity of humans. The long term goal of this study is to broaden the understanding of the pathogenesis of infective endocarditis caused by oral streptococci. We hypothesize that mutans streptococcal cells have specific receptors that bind extracellular matrix molecules and fibrinogen and this interaction functions to facilitate colonization of heart tissue in the pathogenesis of endocarditis caused by mutans streptococci. The goal of this project is to identify and characterize the bacterial cell surface molecules that are involved in the adherence of heart tissue by mutans streptococci. Binding studies in our laboratory have indicated that S. mutans cells have the ability to bind to the human extracellular matrix molecules, fibronectin, laminin, and collagen type I, and the plasma protein, fibrinogen. Also, we have determined that an isogenic antigen I/II (spaF)-deficient mutant strain of S. mutans has a reduced ability to bind fibronectin, collagen and fibrinogen which suggests that antigen I/II contributes to the interaction of S. mutans cells with these molecules. The specific aims of this study are: 1) to clone and characterize genes encoding proteins that mediate the interaction of S. mutans cells with extracellular matrix molecules (fibronectin, taminin and collagen) and fibrinogen; 2) to construct mutant S. mutans strains having defects in their ability to bind extmcellular matrix molecules and fibrinogen; 3) to evaluate using a rat model of experimental endocarditis the role of binding of S. mutans cells to extracellular matrix molecules and fibrinogen in the pathogenesis of infective endocarditis; and 4) to examine the virulence of an antigen I/II(P 1) mutant strain using the rat model of endocarditis. The results of these studies should identify candidate antigens for the production of protective immunity against infective endocarditis caused by oral streptococci as well as provide information on virulence mechanisms that function during infective endocarditis.